Determining oncogenic patterns and cancer predisposition through the transcriptomic profile in Mitchell–Riley syndrome with heterotopic gastric mucosa and duodenal atresia: a case report

Background Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell–Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia. Results We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including “Evading apoptosis” (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), “Proliferation” (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), “Sustained angiogenesis” (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), “Genomic instability” (BAD, BBC3) and “Insensitivity to anti-growth signals” (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as “PI3K signaling”, “ERK signaling”, “JAK-STAT signaling”, “Calcium signaling”, “Other RAS signaling”, “WNT signaling”. Conclusions In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed.

Endoscopic Resection of a Large Polypoid Gastric Heterotopia of Duodenum: a case report

This is a case of gastric heterotopia, a benign condition most commonly found as multiple small polyps in the duodenal bulb, diagnosticated as a large polypoid lesion of the third duodenal portion in a young patient and treated successfully with endoscopic resection under laparoscopic vision.

A66 GASTRIC HETEROTOPIA OF THE COLON IN A PATIENT WITH A POSITIVE FECAL IMMUNOCHEMICAL TEST

Background Gastric heterotopia (GH), indicates the presence of ectopic gastric tissue and is a rare entity outside of the small intestine. Abdominal pain and bleeding are described but most colonic GH is found incidentally. Aims We report a case of colonic GH found on routine screening colonoscopy. Methods Case report and review of the literature. Results Case Report: A 60-year-old woman with a history of alcohol use disorder, chronic Hepatitis C, and gastroesophageal reflux disease was referred for colonoscopy after a positive fecal immunochemical test. Remote colonoscopy was notable for a large tubular adenoma with low-grade dysplasia. The patient denied constitutional symptoms, change in bowel habits, or evidence of gastrointestinal (GI) bleeding. No family history of colorectal cancer was reported. Complete blood count, renal function, electrolytes, and carcinoembryonic antigen were normal. At colonoscopy, a 2 cm sessile polyp (0-Is Paris classification) was identified with a normal vascular pattern, but unclassifiable pit pattern. Submucosal injection was suboptimal suggesting tethering. However, given the history of previous polypectomy and favorable endoscopic appearance, piecemeal resection was attempted and achieved fair results. Histology showed abundant pyloric-type glands with overlying foveolar epithelium (Figure 1). Endoscopic follow-up at 8 months confirmed complete resection. Literature Review GH is observed throughout the GI tract but is predominantly seen in the esophagus and duodenum. Colonic involvement is uncommon with only 12 cases reported. Despite the lack of epidemiological studies, there is a male predominance across all age groups. Pathogenesis is thought to be either congenital, with deposition as the stomach descends during embryogenesis, or acquired secondary to metaplasia following injury to normal intestinal mucosa. Presenting complaints may include altered bowel habits or haematochezia, but most lesions are detected incidentally on surveillance colonoscopy. Endoscopic descriptions are diverse with variations in size (1-60mm), Paris classification (sessile or pedunculated), and appearance (erythematous patch, ulcer, or diverticulum). Endoscopic resection is recommended given association with bleeding but may be technically difficult due to submucosal involvement which may theoretically increase risk of complications such as perforation. Definitive diagnosis rests on histological examination. The risk of malignant transformation of GH in the colon is unknown with only two such cases reported. However, some propose the incidence of malignant change is underestimated as the growing tumor may eliminate the focus of heterotopic gastric mucosa. Conclusions GH in the colon is a rare entity with diverse endoscopic appearances and poorly understood natural history. Careful endoscopic resection is feasible in the absence of other high-risk endoscopic features. Funding Agencies None

Rare Case of Intestinal-Type Adenocarcinoma Arising in Cervical Oesophageal Heterotopic Gastric Mucosa

Heterotopic Gastric Mucosa (HGM) also termed gastric inlet patch or inlet patch, is a rare and benign phenomenon in cervical oesophagus and can be missed during endoscopy. It has an average incidence of 2.5%. Adenocarcinoma arising in the background of gastric heterotopia is very rare and uncommon in the upper oesophagus. A 46-year-old male presented with hoarseness and progressive dysphagia for solids for the past one month. Upper Gastrointestinal Endoscopy (UGIE) revealed a tight stricture at 19-20 cm from the incisors. Initial mucosal biopsies were not conclusive. With high clinical suspicion of malignancy, patient underwent bougie dilation of oesophageal stricture followed by repeat biopsy. Histology revealed an intestinal type of adenocarcinoma, arising in a background of gastric heterotopia of the cervical oesophagus. Alcian Blue/Periodic Acid Schiff (AB/PAS) staining was positive in both the heterotopic glands and in the cancer, indicating the presence of intestinal metaplasia. Tumour cells were immunopositive for cytokeratin-7. A Positron Emission Tomography – Computed Tomography scan revealed a metabolically active lesion located in the upper third of the oesophagus along with uptake in right supraclavicular node. This case report describes a patient with primary intestinal type adenocarcinoma of the cervical oesophagus in the background of HGM not related to Barrett’s oesophagus.